Recent advances in molecular genetics have revealed the benefits of high-throughput sequencing techniques and systematic strategies for studying nucleic acids expressed in a given cell or tissue. These advances have highlighted the need for operator-independent computer-mediated methods for identifying and selecting subsets or individual molecules from complex mixtures of proteins, oligosaccharides and other biomolecules and isolating such selected biomolecules for further analysis.
Strategies for target-driven drug discovery and rational drug design require identifying key cellular components, such as proteins, that are causally related to disease processes and the use of such components as targets for therapeutic intervention. However, present methods of analyzing biomolecules such as proteins are time consuming and expensive, and suffer from inefficiencies in detection, imaging, purification and analysis.
Though the genomics approach has advanced our understanding of the genetic basis of biological processes, it has significant limitations. First, the functions of products encoded by identified genes--and especially by partial cDNA sequences--are frequently unknown. Second, information about post-translational modifications of a protein can rarely be deduced from a knowledge of its gene sequence, and it is now apparent that a large proportion of proteins undergo post-translational modifications (such as glycosylation and phosphorylation) that can profoundly influence their biochemical properties. Third, protein expression is often subject to post-translational control, so that the cellular level of an mRNA does not necessarily correlate with the expression level of its gene product. Fourth, automated strategies for random sequencing of nucleic acids involve the analysis of large numbers of nucleic acid molecules prior to determining which, if any, show indicia of clinical or scientific significance.
For these reasons, there is a need to supplement genomic data by studying the patterns of protein and carbohydrate expression, and of post-translational modification generally, in a biological or disease process through direct analysis of proteins, oligosaccharides and other biomolecules. However, technical constraints have heretofore impeded the rapid, cost-effective, reproducible, systematic analysis of proteins and other biomolecules present in biological samples.